SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma

• Published in: Science translational medicine Vol. 13; no. 591
• Main Authors: Choe, Joseph H, Watchmaker, Payal B, Simic, Milos S, Gilbert, Ryan D, Li, Aileen W, Krasnow, Nira A, Downey, Kira M, Yu, Wei, Carrera, Diego A, Celli, Anna, Cho, Juhyun, Briones, Jessica D, Duecker, Jason M, Goretsky, Yitzhar E, Dannenfelser, Ruth, Cardarelli, Lia, Troyanskaya, Olga, Sidhu, Sachdev S, Roybal, Kole T, Okada, Hideho, Lim, Wendell A
• Format: Journal Article
• Language: English
• Published: United States 28.04.2021
• Subjects: Animals; Brain - metabolism; Brain Neoplasms - therapy; Cell Line, Tumor; Glioblastoma - therapy; Immunotherapy, Adoptive; Mice; Receptors, Antigen, T-Cell - metabolism; T-Lymphocytes - metabolism; Xenograft Model Antitumor Assays

Treatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack of ideal target antigens that are both absolutely tumor specific and homogeneously expressed. We show that multi-antigen prime-and-kill recognition circuits provide flexibility and precision to overcome th...